Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

BACKGROUND: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. METHODS: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. RESULTS: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. CONCLUSIONS: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

Minimal risk of contrast-induced kidney injury in a randomly selected cohort with mildly reduced GFR.

OBJECTIVES: Previous large studies of contrast-induced or post-contrast acute kidney injury (CI-AKI/PC-AKI) have been observational, and mostly retrospective, often with patients undergoing non-enhanced CT as controls. This carries risk of inclusion bias that makes the true incidence of PC-AKI hard to interpret. Our aim was to determine the incidence of PC-AKI in a large, randomly selected cohort, comparing the serum creatinine (Scr) changes after contrast medium exposure with the normal intraindividual fluctuation in Scr. METHODS: In this prospective study of 1009 participants (age 50-65 years, 48% females) in the Swedish CArdioPulmonary bioImage Study (SCAPIS), with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min, all received standard dose intravenous iohexol at coronary CT angiography (CCTA). Two separate pre-CCTA Scr samples and a follow-up sample 2-4 days post-CCTA were obtained. Change in Scr was statistically analyzed and stratification was used in the search of possible risk factors. RESULTS: Median increase of Scr post-CCTA was 0-2 µmol/L. PC-AKI was observed in 12/1009 individuals (1.2%) according to the old ESUR criteria (> 25% or > 44 µmol/L Scr increase) and 2 individuals (0.2%) when using the updated ESUR criteria (≥ 50% or ≥ 27 µmol/L Scr increase). Possible risk factors (e.g., diabetes, age, eGFR, NSAID use) did not show increased risk of developing PC-AKI. The mean effect of contrast media on Scr did not exceed the intraindividual Scr fluctuation. CONCLUSIONS: Iohexol administration to a randomly selected cohort with mildly reduced eGFR is safe, and PC-AKI is very rare, occurring in only 0.2% when applying the updated ESUR criteria. KEY POINTS: • Iohexol administration to a randomly selected cohort, 50-65 years old with mildly reduced eGFR, is safe and PC-AKI is very rare. • Applying the updated ESUR PC-AKI criteria resulted in fewer cases, 0.2% compared to 1.2% using the old ESUR criteria in this cohort with predominantly mild reduction of renal function. • The mean effect of CM on Scr did not exceed the intraindividual background fluctuation of Scr, regardless of potential risk factors, such as diabetes or NSAID use in our cohort of 1009 individuals.

Surveillance of small, solid pulmonary nodules at digital chest tomosynthesis: data from a cohort of the pilot Swedish CArdioPulmonary bioImage Study (SCAPIS).

BACKGROUND: Digital tomosynthesis (DTS) might be a low-dose/low-cost alternative to computed tomography (CT). PURPOSE: To investigate DTS relative to CT for surveillance of incidental, solid pulmonary nodules. MATERIAL AND METHODS: Recruited from a population study, 106 participants with indeterminate solid pulmonary nodules on CT underwent surveillance with concurrently performed CT and DTS. Nodule size on DTS was assessed by manual diameter measurements and semi-automatic nodule segmentations were independently performed on CT. Measurement agreement was analyzed according to Bland-Altman with 95% limits of agreement (LoA). Detection of nodule volume change > 25% by DTS in comparison to CT was evaluated with receiver operating characteristics (ROC). RESULTS: A total of 81 nodules (76%) were assessed as measurable on DTS by two independent observers. Inter- and intra-observer LoA regarding change in average diameter were ± 2 mm. Calculation of relative volume change on DTS resulted in wide inter- and intra-observer LoA in the order of ± 100% and ± 50%. Comparing relative volume change between DTS and CT resulted in LoA of -58% to 67%. The area under the ROC curve regarding the ability of DTS to detect volumetric changes > 25% on CT was 0.58 (95% confidence interval [CI] = 0.40-0.76) and 0.50 (95% CI = 0.35-0.66) for the two observers. CONCLUSION: The results of the present study show that measurement variability limits the agreement between DTS and CT regarding nodule size change for small solid nodules.

The association of body mass index, weight gain and central obesity with activity-related breathlessness: the Swedish Cardiopulmonary Bioimage Study.

INTRODUCTION: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear. METHODS: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. RESULTS: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. CONCLUSION: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

CT colonography: implementation, indications, and technical performance - a follow-up national survey.

BACKGROUND: Computed tomography colonography (CTC) is an accepted complement or alternative to optical colonoscopy (OC) but its implementation is incompletely analyzed, and technical performance varies between centers. PURPOSE: To evaluate implementation, indications, and technical performance of CTC in Sweden and to evaluate compliance to international guidelines. MATERIAL AND METHODS: A structured, self-assessed questionnaire regarding implementation and technical performance of CTC was sent to all eligible radiology departments in Sweden. Eighty-six out of 89 departments replied. Comparisons were made with similar national surveys from 2004 and 2009. RESULTS: The number of centers performing CTC gradually increased from 23 in 2004 to 77 in 2016. In parallel, centers performing barium enema (BE) examinations have decreased from 89 in 2004 to 13 in 2016. Main reasons stated for still performing BE were lack of resources regarding CTC/OC. Main reasons for not performing CTC were lack of suitable software, lack of machine/reading time, and lack of experience. The majority of centers follow international CTC guidelines. An important exception is fecal tagging, which was implemented in only 63% of the centers. Incomplete OC remains a major indication for CTC, while preoperative CTC in colorectal cancer and follow-up after diverticulitis have emerged as new indications. CONCLUSION: CTC today is well implemented in routine healthcare but still lacking in capacity. Indications have expanded over time, and most departments perform "state of the art" CTC, although fecal tagging is incompletely implemented.

Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.

BACKGROUND AND AIMS: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change. METHODS: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS). RESULTS: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women. CONCLUSIONS: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

High prevalence of interstitial lung abnormalities in middle-aged never-smokers.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

Obesity is associated with coronary artery stenosis independently of metabolic risk factors: The population-based SCAPIS study.

BACKGROUND AND AIMS: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. METHODS: In the SCAPIS study (50-65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. RESULTS: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34-1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87-1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. CONCLUSIONS: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.

Artificial intelligence based automatic quantification of epicardial adipose tissue suitable for large scale population studies.

To develop a fully automatic model capable of reliably quantifying epicardial adipose tissue (EAT) volumes and attenuation in large scale population studies to investigate their relation to markers of cardiometabolic risk. Non-contrast cardiac CT images from the SCAPIS study were used to train and test a convolutional neural network based model to quantify EAT by: segmenting the pericardium, suppressing noise-induced artifacts in the heart chambers, and, if image sets were incomplete, imputing missing EAT volumes. The model achieved a mean Dice coefficient of 0.90 when tested against expert manual segmentations on 25 image sets. Tested on 1400 image sets, the model successfully segmented 99.4% of the cases. Automatic imputation of missing EAT volumes had an error of less than 3.1% with up to 20% of the slices in image sets missing. The most important predictors of EAT volumes were weight and waist, while EAT attenuation was predicted mainly by EAT volume. A model with excellent performance, capable of fully automatic handling of the most common challenges in large scale EAT quantification has been developed. In studies of the importance of EAT in disease development, the strong co-variation with anthropometric measures needs to be carefully considered.

Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study.

BACKGROUND: It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. DESIGN: The design of this study was as a cross-sectional analysis from a population-based study cohort. METHODS: From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. RESULTS: Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score >0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score >0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have >1 carotid plaques (1.67 (1.61-1.74)). CONCLUSION: Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.

Visual and Quantitative Evaluation of Emphysema: A Case-Control Study of 1111 Participants in the Pilot Swedish CArdioPulmonary BioImage Study (SCAPIS).

RATIONALE AND OBJECTIVES: Emphysema is a hallmark of chronic obstructive pulmonary disease. The primary aim of this study was to investigate inter- and intraobserver agreement of visual assessment of mild emphysema in low-dose multidetector computed tomography of subjects in the pilot SCAPIS in order to certify consistent detection of mild emphysema. The secondary aim was to investigate the performance of quantitative densitometric measurements in the cohort. MATERIALS AND METHODS: Participants with emphysema (n = 100, 56 males and 44 females) reported in the electronic case report form of pilot SCAPIS and 100 matched controls (gender, age, height, and weight) without emphysema were included. To assess interobserver variability the randomized examinations were evaluated by two thoracic radiologists. For intraobserver variability three radiologists re-evaluated randomized examinations which they originally evaluated. The results were evaluated statistically by Krippendorff's α. The dataset was also assessed quantitively for % lung attenuation value -950 HU (LAV950), mean lung density and total lung volume by commercially available software. RESULTS: Emphysema was visually scored as mild and Krippendorff's α was ≥0.8 for both the inter- and intraobserver agreement regarding presence of emphysema and approaching 0.8 regarding presence and extent of emphysema by location in the upper lobes. Mean LAV950 was not different between the emphysematous and the nonemphysematous participants; 8.3% and 8.4%, respectively. CONCLUSION: The inter- and intraobserver agreement for visual detection of mild emphysema in low-dose multidetector computed tomography was good. Surprisingly, quantitative analysis could not reliably identify participants with mild emphysema, which hampers the use of automatic evaluation.

Concomitant Associations of Healthy Food Intake and Cardiorespiratory Fitness With Coronary Artery Calcium.

Conflicting findings remain regarding associations between lifestyle behaviors and coronary artery calcium (CAC). We investigated concomitant associations of healthy food intake and cardiorespiratory fitness (CRF) with CAC. Data from 706 men and women 50 to 64 years old from the Swedish SCAPIS pilot trial were analyzed. A CAC score was calculated using the Agatston method. A Healthy Food Index (HFI) was established using data from a web-based food frequency questionnaire. CRF was assessed from a bike exercise test. Regression analyses were performed with occurrence of CAC (dichotomous) and level of CAC score in patients with CAC (continuous) as outcomes. 58% had 0 CAC score. HFI was significantly associated with having no CAC (standardized coefficient ß = 0.18, p <0.001) but not with level of CAC score (ß = -0.09, p = 0.34). CRF showed no significant association with having no CAC (ß = -0.08, p = 0.12) or with the level of CAC score (ß = -0.04, p = 0.64). However, there was an interaction between HFI and CRF (ß = -0.23, p = 0.02); for increasing levels of CRF there was stronger negative association between HFI and level of CAC score, reaching ß = -0.48, p = 0.045 for the highest CRF level. In conclusion, these results emphasize the importance of a healthy food intake in combination with higher CRF to counteract CAC development.

Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects.

OBJECTIVES: This study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors. METHODS: The study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50-64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation ≤40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models. RESULTS: NAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07-2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0-1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13-16.6). CONCLUSIONS: NAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.

Absolute lung size and the sex difference in breathlessness in the general population.

BACKGROUND: Breathlessness is associated with major adverse health outcomes and is twice as common in women as men in the general population. We evaluated whether this is related to their lower absolute lung volumes. METHODS: Cross-sectional analysis of the population-based Swedish CardioPulmonarybioImage Study (SCAPIS) Pilot, including static spirometry and diffusing capacity (n = 1,013; 49% women). Breathlessness was measured using the modified Medical Research Council (mMRC) scale and analyzed using ordinal logistic regression adjusting for age, pack-years of smoking, body mass index, chronic airway limitation, asthma, chronic bronchitis, depression and anxiety in all models. RESULTS: Breathlessness was twice as common in women as in men; adjusted odds ratio (OR) 2.20 (95% confidence interval, 1.32-3.66). Lower absolute lung volumes were associated with increased breathlessness prevalence in both men and women. The sex difference in breathlessness was unchanged when adjusting for lung function in %predicted, but disappeared when controlling for absolute values of total lung capacity (OR 1.12; 0.59-2.15), inspiratory capacity (OR 1.26; 0.68-2.35), forced vital capacity (OR 0.84; 0.42-1.66), forced expiratory volume in one second (OR 0.70; 0.36-1.35) or lung diffusing capacity (OR 1.07; 0.58-1.97). CONCLUSION: In the general population, the markedly higher prevalence of breathlessness in women is related to their smaller absolute lung volumes.

Androgens and glucuronidated androgen metabolites are associated with metabolic risk factors in men.

CONTEXT: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear. OBJECTIVE: Our objective was to determine the predictive value of serum levels of androgens and glucuronidated androgen metabolites for metabolic risk factors. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two Swedish cohorts (1,068 young adult and 1,001 elderly men). MAIN OUTCOME MEASURES: We measured correlation of serum dihydrotestosterone (DHT), testosterone (T), and glucuronidated androgen metabolites with fat mass, fat distribution, serum lipids, and insulin resistance. RESULTS: Both DHT and T were negatively associated with different measures of fat mass in both cohorts (P < 0.001). Further statistical analysis indicated that DHT, but not T, was independently negatively associated with different measures of fat mass and insulin resistance (P < 0.001). The glucuronidated androgen metabolite androstane-3alpha,17beta-diol-17glucuronide (17G) was independently positively associated with fat mass (P < 0.001). Most importantly, the 17G to DHT ratio was strongly correlated, not only with fat mass but also with central fat distribution, intrahepatic fat, disturbed lipid profile, insulin resistance, and diabetes, explaining a substantial part of the total variance in total body fat (12% in young adult men, 15% in elderly men), the homeostasis model assessment index (10%), and high-density lipoprotein cholesterol (7%). CONCLUSION: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3alpha,17beta-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G to DHT ratio as a metabolic risk factor in men.

Pubertal timing is an independent predictor of central adiposity in young adult males: the Gothenburg osteoporosis and obesity determinants study.

The role of puberty and normal variations in pubertal timing for the development of obesity in men is unclear. The aim of the current study was to investigate the impact of pubertal timing and prepubertal BMI (kg/m(2)) for young adult BMI and fat mass distribution. Detailed growth charts from birth to age 18-20 years were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity (PHV) and BMI at age 10 years were estimated for 579 subjects, and PHV was used as an assessment of pubertal timing. The fat mass characterization and distribution were analyzed using dual X-ray absorptiometry and peripheral as well as abdominal computed tomography at age 18.9 +/- 0.5 years. We demonstrate that age at PHV is an independent negative predictor of young adult BMI and whole-body fat mass. Interestingly, age at PHV is an independent negative predictor of central, but not peripheral, fat mass. In contrast, BMI at 10 years of age predicts both central and peripheral subcutaneous fat mass. In conclusion, we demonstrate that early pubertal onset specifically predicts a central fat mass distribution, while a predominantly subcutaneous obese phenotype is strongly predicted by a high prepubertal BMI.

Validity of physician-diagnosed COPD in relation to spirometric definitions of COPD in a general population aged 50-64 years - the SCAPIS pilot study.

BACKGROUND: In epidemiological studies, items about physician-diagnosed COPD are often used. There is a lack of validation and standardization of these items. MATERIALS AND METHODS: In a general population-based study, 1,050 subjects completed a questionnaire and performed spirometry, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) after inhalation of 400 µg of salbutamol. COPD was defined as the ratio of FEV1/FVC <0.7 after bronchodilation. Physician-diagnosed COPD was defined as an affirmative answer to the single item: "Have you ever had COPD diagnosed by a physician?", physician-diagnosed COPD/emphysema as an affirmative answer to any of the two single items; "Have you ever had COPD diagnosed by a physician?" or "Have you ever been told by a physician that you have emphysema?", physician-diagnosed chronic bronchitis as an affirmative answer to; "Have you ever been told by a physician that you have chronic bronchitis?" and physician-diagnosed COPD, emphysema or chronic bronchitis was defined as an affirmative answer to either of the three items above. RESULTS: For the single item about physician-diagnosed COPD, the sensitivity was around 0.11 and the specificity was almost 0.99 in relation to COPD. The sensitivity of the combined items about COPD/emphysema in detecting COPD was 0.11 and the specificity was high, 0.985. When the items about physician-diagnosed COPD, emphysema or chronic bronchitis were merged as one entity, the sensitivity went up (0.13) and the specificity went down (0.95). CONCLUSION: Items about physician-diagnosed COPD have low sensitivity but a very high specificity, indicating that these items will minimize the proportion of false positives. The low sensitivity will underestimate the total burden of COPD in the general population. Items about physician-diagnosed COPD may be used in studies of risk factors for COPD, but are not recommended in prevalence studies.

Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies.

Computed Tomography (CT) allows detailed studies of body composition and its association with metabolic and cardiovascular disease. The purpose of this work was to develop and validate automated and manual image processing techniques for detailed and efficient analysis of body composition from CT data. The study comprised 107 subjects examined in the Swedish CArdioPulmonary BioImage Study (SCAPIS) using a 3-slice CT protocol covering liver, abdomen, and thighs. Algorithms were developed for automated assessment of liver attenuation, visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, thigh muscles, subcutaneous, subfascial (SFAT) and intermuscular adipose tissue. These were validated using manual reference measurements. SFAT was studied in selected subjects were the fascia lata could be visually identified (approx. 5%). In addition, precision of manual measurements of intra- (IPAT) and retroperitoneal adipose tissue (RPAT) and deep- and superficial SAT was evaluated using repeated measurements. Automated measurements correlated strongly to manual reference measurements. The SFAT depot showed the weakest correlation (r = 0.744). Automated VAT and SAT measurements were slightly, but significantly overestimated (≤4.6%, p ≤ 0.001). Manual segmentation of abdominal sub-depots showed high repeatability (CV ≤ 8.1%, r ≥ 0.930). We conclude that the low dose CT-scanning and automated analysis makes the setup suitable for large-scale studies.

Occupational exposure to vapor, gas, dust, or fumes and chronic airflow limitation, COPD, and emphysema: the Swedish CArdioPulmonary BioImage Study (SCAPIS pilot).

BACKGROUND: The aim of this study was to estimate the occupational burden of airflow limitation, chronic airflow limitation, COPD, and emphysema. MATERIALS AND METHODS: Subjects aged 50-64 years (n=1,050) were investigated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Airflow limitation was defined as FEV1/FVC <0.7 before bronchodilation. Chronic airflow limitation was defined after bronchodilation either according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as FEV1/FVC <0.7 or according to the lower limit of normal (LLN) approach as FEV1/FVC < LLN. COPD was defined as chronic airflow limitation (GOLD) in combination with dyspnea, wheezing, or chronic bronchitis. Emphysema was classified according to findings from computed tomography of the lungs. Occupational exposure was defined as self-reported occupational exposure to vapor, gas, dust, or fumes (VGDF). Odds ratios (OR) were calculated in models adjusted for age, gender, and smoking; population-attributable fractions and 95% CI were also calculated. RESULTS: There were significant associations between occupational exposure to VGDF and COPD (OR 2.7, 95% CI 1.4-51), airflow limitation (OR 1.8, 95% CI 1.3-2.5), and emphysema (OR 1.8, 95% CI 1.1-3.1). The associations between occupational exposure to VGDF and chronic airflow limitation were weaker, and for the OR, the CIs included unity. The population-attributable fraction for occupational exposure to VGDF was 0.37 (95% CI 0.23-0.47) for COPD and 0.23 (95% CI 0.05-0.35) for emphysema. CONCLUSION: The occupational burden of COPD and computed tomography-verified emphysema is substantial.